Host metabolic responses to SARS-CoV-2 and influenza viruses: parallels and contrasts.

BACKGROUND

SARS-CoV-2 and Influenza virus are two major respiratory viruses, responsible for the COVID-19 and the flu respectively. To achieve their replication, these viruses do not merely hijack host cells; they reprogram them, and the host's metabolism is no exception.

AIM OF THE REVIEW: This review explores how two major respiratory pathogens, SARS-CoV-2 and influenza virus, manipulate host metabolism to fuel their replication and drive disease.

KEY SCIENTIFIC CONCEPTS OF THE REVIEW: Despite differences in their genome organization and replication strategies, both viruses disrupt central metabolic pathways, including glucose processing, the Krebs cycle, amino acid and nucleotide synthesis. Common effects include enhanced anaerobic glycolysis, depletion of key amino acids, activation of the kynurenine pathway, and disruption of purine signaling. However, each virus leaves a distinct metabolic fingerprint. SARS-CoV-2 infection leads to glucose accumulation, alters late-stage Krebs cycle metabolites, and significantly disrupts nucleotide production. In contrast, influenza viral infection depletes glucose and dampens Krebs cycle activity, with a less consistent impact on nucleotide pathways. Viral proteins, such as SARS-CoV-2 ORF3a and influenza virus NS1, play a crucial role in these metabolic shifts. These changes not only reflect viral strategies but also correlate with disease severity. As metabolomics technologies advance, understanding these virus-specific and shared metabolic changes could unlock new diagnostic tools, prognostic markers, and treatment strategies.